We have a long-standing interest in studying mechanisms of organ/tissue interactions that maintain homeostatic balance and, on the other hand, dynamically respond to disturbances.
The lymphatic system presents an excellent model for studying short- and long-range tissue interactions in the context of adaptive immunity since lymphatics connect peripheral tissues to systemic circulation via tissue fluid draining and leukocyte trafficking. Further, the interactions between tissue compartments and cell types are dynamic and amenable to live-imaging approaches.
Recent years have revolutionized our understanding of the role of the lymphatic system in the control of adaptive immunity. To start an adaptive immune response, lymphatic vessel endothelium actively recruits antigen-presenting dendritic cells, to the lymphatic vessel lumen and, subsequently, guides them into the lymph nodes. In the lymph nodes, dendritic cells present the antigens and activate pathogen-specific T cells.
Our research group focuses on two key events that are essential for efficient antigen delivery into the lymph nodes. First, we explore how sprouting lymphangiogenesis is controlled to yield a well-structured functional lymphatic vessel network. Second, we investigate how lymphatic endothelium guides dendritic cell entry into the lymphatic system. To address these questions, we use in vivo models, tissue explants, primary cell co-culture assays, and state-of-the-art microscopy.
We expect that our studies form a basis for strategies to treat patients suffering from diseases in which inflammation is an essential component.
Current Group members
Kari Vaahtomeri, Principal investigator, Ph.D. Doc.
Inam Liaqat, Doctoral student
Maria Saario, Doctoral student
Jeremia Saari, Doctoral student
Mario Karam, Doctoral student
Emmi Tiilikainen, completed M.Sc. thesis in the group
Sonja Granroth, completed M.Sc. thesis in the group
Emma Jakobsson, completed M.Sc. thesis in the group
Ida Hilska, completed M.Sc. thesis in the group
Spatially targeted chemokine exocytosis guides transmigration at lymphatic endothelial multicellular junctions. Liaqat I., Hilska I., Jakobsson E., Saario M., Crivaro M., Peränen J., Vaahtomeri K. The EMBO Journal. 43(15):3141-3174, 2024
DLL4-Notch3-WNT5B axis mediates bi-directional pro-metastatic crosstalk between melanoma and lymphatic endothelial cells. Alve S., Gramolelli S., Jukonen J., Juteau S., Pink A., Manninen A., Monto E., Lackman MH., Carpén O., Karaman S., Saharinen P., Vaahtomeri K. and Ojala PM.
JCI insight, 9(1):e171821, 2023.
Self-organized and directed branching results in optimal coverage in developing dermal lymphatic networks. Can Ucar M., Hannezo E. , Tiilikainen E., Liaqat I., Jakobsson E., Nurmi, H., Vaahtomeri K. Nature Communications, 21;14(1):5878, 2023
Lymphangiogenesis requires Ang2/Tie/PI3K signaling for VEGFR3 cell surface expression. Korhonen E. A., Murtomäki A., Jha S.K., Anisimov A., Pink A., Zhang Y., Stritt S., Liaqat I., Stanczuk L., Alderfer L., Sun Z., Kapiainen E., Singh A., Sultan I., Lantta A., Leppänen V.M., Eklund L., He Y., Augustin H.G., Vaahtomeri K., Saharinen P., Mäkinen T., Alitalo K. 1 Aug 2022, J Clin Invest., 132(15):e155478.
Shape and function of interstitial chemokine CCL21 gradients are independent of heparan sulfates produced by lymphatic endothelium. Vaahtomeri K., Moussion C., Hauschild R., Sixt M. 25 Feb 2021, Front Immunol. 12:630002, 2021.
Locally triggered release of chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia. Vaahtomeri K, Brown M, Hauschild R, De Vries I, Leithner AF, Mehling M, Kaufmann WA, Sixt M. 2 May 2017, Cell Reports, 19(5):902-909.
CCL21 promotes tissue egress of intralymphatic dendritic cells through afferent lymphatic vessels. Russo E., Teijeira A., Vaahtomeri K., Wilbrodt, AH., Bloch, JS., Nitschke, M., Santambrogio, L., Kerjaschki, D., Sixt, M., Halin, C.”, 23 February 2016, Cell Reports, 14(7):1723-1734.
Dendritic cells interpret Haptotactic Chemokine Gradients in a manner governed by signal-to-noise ratio and dependent on GRK6. Schwarz J, Bierbaum V, Vaahtomeri K, Hauschild R, Brown M, de Vries I, Leithner A, Reversat A, Merrin J, Tarrant T, Bollenbach T, Sixt M. 8 May 2017, Current Biology, 27(9):1314-1325.
Lymphatic exosomes promote dendritic cell migration along guidance cues. Brown M, Johnson LA, Leone DA, Majek P, Vaahtomeri K, Senfter D, Bukosza N, Schachner H, Asfour G, Langer B, Hauschild R, Parapatics K, Hong YK, Bennett KL, Kain R, Detmar M, Sixt M, Jackson DG, Kerjaschki D. 4 June 2018, Journal of cell biology, 217(6):2205-2221.
